Increase In Pulmonary Arterial Pressure Research Articles

Hemodynamic Mechanisms of Exercise-Induced Pulmonary Hypertension in Patients with Lymphangioleiomyomatosis: The Role of Exercise Stress Echocardiography

The pathogenesis of pulmonary hypertension (PH) in lymphangioleiomyomatosis (LAM) has not yet been completely clarified. The aim of this study was to conduct a noninvasive evaluation of the main hemodynamic mechanisms of exercise-induced PH in patients with LAM, assessed using exercise stress echocardiography. Fifteen patients with LAM (mean age, 47±13years; all women) without resting PH were enrolled in a prospective single-center study and compared with 15 healthy female control subjects (mean age, 45.2±8years; P=.65). A complete echocardiographic study with Doppler tissue imaging was performed at baseline and during semisupine symptom-limited exercise testing to evaluate (1) left ventricular systolic and diastolic function, (2) right ventricular contractile function, (3) estimated pulmonary capillary wedge pressure, (4) estimated systolic and mean pulmonary artery pressure, and (5) estimated pulmonary vascular resistance. Compared with healthy control subjects, patients with LAM during exercise showed echocardiographic signs of right ventricular overload and right ventricular systolic dysfunction and significant increases in mean pulmonary artery pressure (14.4±6.5 vs 4.2±3.1mm Hg, P<.0001), pulmonary vascular resistance(+68.3±42.1 vs -0.1±18.3 dyne-sec/cm5, P<.0001), and, unexpectedly, pulmonary capillary wedge pressure (+8.3±5.3 vs -0.5±1.3mm Hg, P<.0001). Exercise-induced PH in patients with LAM could be related not only to hypoxic pulmonary vascular vasoconstriction during exercise (precapillary PH) but also to a significant exercise-induced increase in estimated pulmonary capillary wedge pressure, probably secondary to diastolic dysfunction (postcapillary PH).

Systolic pulmonary artery pressure assessed during routine exercise Doppler echocardiography: insights of a real-world setting in patients with elevated pulmonary pressures.

Pulmonary hypertension is a marker of disease severity. Exercise Doppler echocardiography (EDE) has proven to be feasible and reliable to assess pulmonary pressure. Increase in systolic pulmonary artery pressure (sPAP) has diagnostic and prognostic value in controlled studies. However, its value when assessed during routine examination in patients with cardiopulmonary diseases and resting sPAP > 35mmHg is not clearly defined. Clinical documentation and offline reevaluation of digitally stored EDE examinations of patients with appropriate clinical indications for EDE were analyzed. N = 278 patients with sPAP at rest > 35mmHg met inclusion criteria. One patient was lost to follow-up. Mean age of patients was 72 ± 10 years, 178 (64%) of the study population were men. There were no relevant differences among survivors and non-survivors concerning comorbidities. Exercise performance (3.6 ± 1.2 vs. 4.9 ± 1.4 MET, p < 0.001) was lower, whereas sPAP during exercise was higher (67.3 ± 14.7 vs. 62.1 ± 13.2mmHg, p = 0.027) in non-survivors. Univariate predictors of all-cause mortality were NYHA functional class III (HR = 2.56, p < 0.001), ≥ 2-vessels coronary artery disease (CAD) (HR = 1.93, p = 0.04), left atrial diameter > 45mm (HR = 2.58, p < 0.001), rest sPAP > 42mmHg (HR = 1.94, p = 0.010) and ΔsPAP increase ≥ 0.23mmHg/Watt (HF = 1.92, p = 0.010). After multivariate analysis, NYHA functional class III (HR = 2.35, p < 0.001), LA diameter (HR = 2.28, p = 0.003) and sPAP increase ≥ 0.23mmHg/Watt (HF = 2.19, p = 0.002) remained significant predictors of mortality, whereas a double product (HR = 0.42, p = 0.005) was associated with better prognosis. sPAP assessment during routine EDE provides relevant prognostic information comparable to findings in studies in selected populations. A higher sPAP increase at lower exercise performance shows significant association with increased of mortality.

Stem cell therapy targeting the right ventricle in pulmonary arterial hypertension: is it a potential avenue of therapy?

Pulmonary arterial hypertension (PAH) is an incurable disease characterized by an increase in pulmonary arterial pressure due to pathological changes to the pulmonary vascular bed. As a result, the right ventricle (RV) is subject to an increased afterload and undergoes multiple changes, including a decrease in capillary density. All of these dysfunctions lead to RV failure. A number of studies have shown that RV function is one of the main prognostic factors for PAH patients. Many stem cell therapies targeting the left ventricle are currently undergoing development. The promising results observed in animal models have led to clinical trials that have shown an improvement of cardiac function. In contrast to left heart disease, stem cell therapy applied to the RV has remained poorly studied, even though it too may provide a therapeutic benefit. In this review, we discuss stem cell therapy as a treatment for RV failure in PAH. We provide an overview of the results of preclinical and clinical studies for RV cell therapies. Although a large number of studies have targeted the pulmonary circulation rather than the RV directly, there are nonetheless encouraging results in the literature that indicate that cell therapies may have a direct beneficial effect on RV function. This cell therapy strategy may therefore hold great promise and warrants further studies in PAH patients.

Acute Changes on Pulmonary Pressure Following Percutaneous Closure of Secundum Atrial Septal Defect

Pulmonary hypertension is a common complication of congenital heart disease due to systemic – pulmonary circulation shunt which if left uncorrected leads to increased pulmonary artery pressure, vascular remodeling and further increase of pulmonary vascular resistance. Percutaneous closure of the defect interrupts this shunt thus reducing right heart and pulmonary circulation load and pulmonary artery pressure. In this paper we present two cases of percutaneous secundum atrial septal defect closure complicated by pulmonary hypertension along with echocardiographic evaluation of cardiopulmonary hemodynamic changes before and shortly after device closure. Forty years old and thirty three years old females presented to our clinics with classical symptoms of atrial septal defects, assessment revealed TVG of 37 mmHg and 30 mmHg,shortly after the procedure patient was re-evaluated and revealed TVG of 39 mmHg and 23 mmHg respectively. From these cases we conclude that changes in pulmonary artery pressure is not constantly found after device closure. However both patients display improvements in functional capabilities.

Daily chronic intermittend hypobaric hypoxia does not induce chronic increase in pulmonary arterial pressure

Daily chronic intermittend hypobaric hypoxia does not induce chronic increase in pulmonary arterial pressure

Inhaled hexadecyl-treprostinil provides pulmonary vasodilator activity at significantly lower plasma concentrations than infused treprostinil

INS1009 is a long acting pulmonary vasodilator prodrug of treprostinil (TRE) that is formulated in a lipid nanoparticle for inhaled delivery by nebulization. This study examined the ability of INS1009 to inhibit vasoconstriction in the pulmonary vasculature of rats and dogs and the extent to which local activity within the lung contributes to its activity. Rats received a single dose of INS1009 by nose-only inhalation or were given a continuous intravenous (i.v.) infusion of TRE, followed by an i.v. challenge of the thromboxane mimetic pulmonary vasoconstrictor U46619 and the increase in pulmonary arterial pressure (PAP) was measured. In beagle dogs, INS1009 was given by inhalation via face mask and TRE was given by continuous i.v. infusion; vasoconstriction was then induced by inhaled hypoxia with reduction of FIO2 to 0.10. Changes in the dog's right ventricular pulse pressure (RVPP) were measured using implanted telemetry probes. Blood samples were collected in rats and dogs immediately after the challenge to measure the plasma TRE concentration. Exposure of rats to inhaled INS1009 (0.5, 3.0 and 20.9 μg/kg) inhibited the U46619-induced increase in PAP at all doses up to 6 h with statistically significant inhibition up to 24 h with the pooled dose-response data. The concentration of TRE in the plasma at which PAP was reduced by 50% was approximately 60-fold lower for INS1009 (EC50 = 0.08 ng/mL) as compared to i.v. TRE (EC50 = 4.9 ng/mL). In dogs, INS1009 (2.7–80.9 μg/kg) inhibited the hypoxia-induced increase in RVPP at all doses up to 6 h with activity once again observed with the pooled dose-response of 10 μg/kg and higher at 24 h. The concentration of TRE in the plasma at which RVPP was reduced by 50% was approximately 550-fold lower for INS1009 (EC50 = 0.0075 ng/mL) as compared to i.v. TRE (EC50 = 4.1 ng/mL). These studies, in two species and by two different pulmonary vasoconstrictor challenges, demonstrate that inhaled INS1009 not only has long-acting vasodilatory effects but also that the local activity within the lung contributes to this response. Therefore, INS1009 may offer the opportunity to effect pulmonary vasodilation for long periods but with substantially lower systemic exposure than infused TRE.

Hemodynamic Characteristics in Significant Symptomatic and Asymptomatic Primary Mitral Valve Regurgitation at Rest and During Exercise.

In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery. Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm2; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg; P=0.003) and at maximal exercise (30±6 versus 25±7 mm Hg; P=0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg; P=0.005) and maximal exercise (46±8 versus 39±7 mm Hg; P=0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction (r=-0.52; P=0.02) and right ventricular ejection fraction (r=-0.67; P<0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure. Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02961647.

Catheter‐based edge‐to‐edge mitral valve repair for pulmonary pressure reduction and to postpone heart transplantation in a teenaged patient

We report a case of catheter‐based edge‐to‐edge mitral valve repair in a teenage male patient with non‐ischaemic cardiomyopathy to improve pulmonary hypertension secondary to severe functional mitral regurgitation (FMR) to defer anticipated heart transplantation. A 19‐year‐old patient with previous history of fulminant myocarditis followed by markedly left ventricular dysfunction presented with severe mitral regurgitation 3 years after initial recovery. Slightly over time, deterioration of FMR was associated with gradual increase in pulmonary artery pressures despite optimal medical therapy. MitraClip implantation in this young patient was successfully performed with sustainable improvement of pulmonary hypertension.

Right Ventricular Perfusion: Physiology and Clinical Implications.

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

Daily Chronic Intermittent Hypobaric Hypoxia Does Not Induce Chronic Increase in Pulmonary Arterial Pressure Assessed by Echocardiography.

Chronic hypoxia causes pulmonary vascular remodeling resulting in persistently increased pulmonary arterial pressures (PAP) even after return to normoxia. Recently, interest in chronic intermittent hypobaric hypoxia (CIHH) was raised because it occurs in subjects working at high altitude (HA) but living in lowland. However, effects of daily CIHH on PAP are unknown. In this pilot study, we included 8 healthy subjects working at (2650 m) each workday for 8-9 h while living and sleeping at LA and 8 matched control subjects living and working at LA. Cardiorespiratory measurements including echocardiography at rest and during exercise were performed at LA (Munich, 530 m) and HA (Zugspitze, 2650 m). Hemoglobin was higher in CIHH subjects. LA echocardiography showed normal right and left cardiac dimensions and function in all subjects. Systolic PAP (sPAP) and tricuspid annular plane systolic excursion (TAPSE) at rest were similar in both groups. Resting blood gas analysis (BGA) at HA revealed decreased pCO2 in CIHH compared to controls (HA: 28.4 versus 31.7 mmHg, p=0.01). During exercise, sPAP was lower in CIHH subjects compared to controls (LA: 28.7 versus 35.3 mmHg, p=0.02; HA: 26.3 versus 33.6 mmHg, p=0.04) and peripheral oxygen saturation (SpO2) was higher. In sum, subjects exposed to CIHH showed no signs of pulmonary vascular remodeling.

Heart-lung interactions in acute respiratory distress syndrome: pathophysiology, detection and management strategies.

Acute respiratory distress syndrome (ARDS) is the most severe form of acute respiratory failure characterized by diffuse alveolar and endothelial damage. The severe pathophysiological changes in lung parenchyma and pulmonary circulation together with the effects of positive pressure ventilation profoundly affect heart lung interactions in ARDS. The term pulmonary vascular dysfunction (PVD) refers to the specific involvement of the vascular compartment in ARDS and is expressed clinically by an increase in pulmonary arterial (PA) pressure and pulmonary vascular resistance both affecting right ventricular (RV) afterload. When severe, PVD can lead to RV failure which is associated to an increased mortality. The effect of PVD on RV function is not only a consequence of increased pulmonary vascular resistance as afterload is a much more complex phenomenon that includes all factors that oppose efficient ventricular ejection. Impaired pulmonary vascular mechanics including increased arterial elastance and augmented wave-reflection phenomena are commonly seen in ARDS and can additionally affect RV afterload. The use of selective pulmonary vasodilators and lung protective mechanical ventilation strategies are therapeutic interventions that can ameliorate PVD. Prone positioning and the open lung approach (OLA) are especially attractive strategies to improve PVD due to their effects on increasing functional lung volume. In this review we will describe some pathophysiological aspects of heart-lung interactions during the ventilatory support of ARDS, its clinical assessment and discuss therapeutic interventions to prevent the occurrence and progression of PVD and RV failure.

Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice.

Pulmonary embolism (PE) results from deep vein thrombosis (DVT) and can lead to chronic thromboembolic pulmonary hypertension (CTEPH) involving vascular dysfunction. Mechanisms are incompletely understood, in part due to lack of mouse models. We induced PE in C57BL/6 mice by intravenous injection of thrombin (166 U/kg BW), confirmed by a sudden bradycardia, bradypnea, and an increase in pulmonary artery (PA) pressure observed by high-frequency ultrasound. While symptoms resolved rapidly after single thrombin application, repeated PEs resulted in sustained PA-pressure increase, increased PA superoxide formation assessed by oxidative fluorescent microtopography, increased PA gp91phox expression, and endothelial dysfunction assessed by isometric tension studies of isolated PA segments after 24 hours. DVT was modeled in C57BL/6 mice by ligation of the inferior vena cava (IVC). Importantly, small pulmonary emboli could be detected along with a mild phenotype of PA endothelial dysfunction and oxidative stress in the absence of PA-pressure elevation. mRNA expression of plasminogen activator inhibitor-1 was increased in PAs of mice with recurrent PE after repetitive thrombin injections and to a lesser extent in DVT mice. In summary, our data suggest that PA endothelial dysfunction, induced by gp91phox-derived ROS, is an early event upon repetitive PE. This phenomenon might help to elucidate the mechanisms of PA dysfunction in the pathogenesis of CTEPH.

Modeling Pulmonary Hypertension: A Pig Model of Postcapillary Pulmonary Hypertension.

Pulmonary hypertension (PH) is a pathophysiological condition defined as an increase in mean pulmonary arterial pressure ≥25mmHg at rest assessed by right heart catheterization.Based on hemodynamic criteria, precapillary PH is characterized by a mean pulmonary capillary wedge pressure ≤15mmHg as opposed to the postcapillary PH by >15mmHg. Postcapillary PH is one of the most common forms of PH, often caused by left ventricular dysfunction and heart failure.In this chapter, we describe protocols for creating a large animal model of postcapillary PH. It is induced by open chest surgery (lateral thoracotomy) to band the pulmonary veins. The model is characterized by low mortality, relatively easy surgical procedure with well reproducible results, and pulmonary and cardiac remodeling at the structural, functional, and molecular levels. The presence of right ventricular (RV) remodeling is of significant importance since right heart failure is the main cause of death in patients suffering from PH. One of the advantages of the model described in this chapter is that both adaptive and maladaptive forms of RV remodeling can be observed during the progression of the disease. This can help understand the progressive pathophysiology of RV failure in humans. Besides the description of the model, a detailed guidance of the RV functional assessment in pigs forboth invasive (heart catheterization) and noninvasive (echocardiography) approachesis provided.

Elevated Mean Pulmonary Artery Pressure and Right Ventricular Dysfunction in Children with Chronic Kidney Disease.

Background:Elevated mean pulmonary artery pressure (mPAP) and right heart failure increase mortality in patients with chronic kidney disease (CKD).Objectives:The objective of this study is to determine the prevalence of elevated mPAP in children with CKD compared with matched controls and to ascertain the relationship between elevated mPAP with right ventricular dysfunction and history of hemodialysis.Materials and Methods:A cross-sectional comparative study of mPAP and tricuspid annular plane systolic excursion of 21 children with CKD and age- and sex-matched controls asymptomatic for cardiac disease was conducted.Results:Median mPAP was 27.69 (18.3–36.1) mmHg in CKD patients compared with 14.55 (13.5–17.1) mmHg in controls (P = 0.002). Elevated mPAP was present in 42.9% of CKD group and 0% in controls (P < 0.001). The prevalence of right ventricle (RV) dysfunction in CKD was 9.5% and 0% in controls (P = 0.49). Right ventricular dysfunction was significantly more common in patients with elevated mPAP compared with those with normal mPAP (P < 0.001). Children with CKD who had a history of having been dialyzed were less likely to have elevated mPAP (P < 0.001).Conclusion:Elevated mPAP is significantly more common in children with CKD compared with controls. CKD population with mPAP elevation is more likely to have impaired RV function. The occurrence of elevated mPAP was more common in those who were never dialyzed.

Image-based computational assessment of vascular wall mechanics and hemodynamics in pulmonary arterial hypertension patients

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevated pulmonary arterial (PA) pressure. While several computational hemodynamic models of the pulmonary vasculature have been developed to understand PAH, they are lacking in some aspects, such as the vessel wall deformation and its lack of calibration against measurements in humans. Here, we describe a computational modeling framework that addresses these limitations. Specifically, computational models describing the coupling of hemodynamics and vessel wall mechanics in the pulmonary vasculature of a PAH patient and a normal subject were developed. Model parameters, consisting of linearized stiffness E of the large vessels and Windkessel parameters for each outflow branch, were calibrated against in vivo measurements of pressure, flow and vessel wall deformation obtained, respectively, from right-heart catheterization, phase-contrast and cine magnetic resonance images. Calibrated stiffness E of the proximal PA was 2.0 and 0.5 MPa for the PAH and normal models, respectively. Calibrated total compliance CT and resistance RT of the distal vessels were, respectively, 0.32 ml/mmHg and 11.3 mmHg∗min/l for the PAH model, and 2.93 ml/mmHg and 2.6 mmHg∗min/l for the normal model. These results were consistent with previous findings that the pulmonary vasculature is stiffer with more constricted distal vessels in PAH patients. Individual effects on PA pressure due to remodeling of the distal and proximal compartments of the pulmonary vasculature were also investigated in a sensitivity analysis. The analysis suggests that the remodeling of distal vasculature contributes more to the increase in PA pressure than the remodeling of proximal vasculature.

New pulmonary hypertension model in conscious dogs to investigate pulmonary-selectivity of acute pharmacological interventions.

Testing of investigational drugs in animal models is a critical step in drug development. Current models of pulmonary hypertension (PH) have limitations. The most relevant outcome parameters such as pulmonary artery pressure (PAP) are measured invasively which requires anesthesia of the animal. We developed a new canine PH model in which pulmonary vasodilators can be characterized in conscious dogs and lung selectivity can be assessed non-invasively. Telemetry devices were implanted to measure relevant hemodynamic parameters in conscious dogs. A hypoxic chamber was constructed in which the animals were placed in a conscious state. By reducing the inspired oxygen fraction (FiO2) to 10%, a hypoxic pulmonary vasoconstriction was induced leading to PH. The PDE-5 inhibitor sildenafil, the current standard of care was compared to atrial natriuretic peptide (ANP). The new hypoxic chamber provided a stable hypoxic atmosphere during all experiments. The mean PAP under normoxic conditions was 15.8±1.8mmHg. Hypoxia caused a reliable increase in mean PAP (+ 12.2±3.2mmHg, p < 0.0001). Both, sildenafil (- 6.8±4.4mmHg) and ANP (- 6.4±3.8mmHg) significantly (p < 0.05) decreased PAP. Furthermore sildenafil and ANP showed similar effects on systemic hemodynamics. In subsequent studies, the in vitro effects and gene expression pattern of the two pathways were exemplified. By combining the hypoxic environment with the telemetric approach, we could successfully establish a new acute PH model. Sildenafil and ANP demonstrated equal effects regarding pulmonary selectivity. This non-invasive model could help to rapidly screen pulmonary vasodilators with decreased animal burden.

Abstract 21287: Myocardial Oxygen Delivery is Progressively Impaired During Development of Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) increases afterload of the right ventricle (RV), initially resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood. Hypothesis: The increased workload together with the RV hypertrophy increases oxygen demand of the myocardium, which is insufficiently compensated by an increase in myocardial oxygen supply through the right coronary vasculature. This mismatch between oxygen supply and demand is exacerbated during physical activity when oxygen demand increases. Methods: PH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (CBF) rest and during graded treadmill exercise. Results: Pulmonary venous banding (PVB) resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 29±1 mmHg (week 5) and 39±3 mmHg (week 12); CON 20±1 mmHg and 21±1 mmHg, both P&lt;0.05) that was accompanied by RV hypertrophy (RV/bodyweight 1.18±0.05 (CON), 1.70±0.15 (PVB), P=0.06). The relation between myocardial oxygen delivery (CBF*arterial oxygen content) and Myocardial work (heartrate*pulmonary artery pressure) was not different between CON and PVB at week 5 , but rotated downwards at week 12 weeks (Figure), indicative of a mismatch between oxygen supply and demand. Histology revealed an increase in cardiomyocyte size (717±35 vs 598±30 μm 2 , P&lt;0.05), whereas capillary density and interstitial fibrosis were not changed. Conclusions: Progression of PH leads to a mismatch between myocardial oxygen supply and demand, particularly during exercise. This mismatch between supply and demand may cause myocardial ischemia and contribute to the transition of RV hypertrophy to failure.

An official European Respiratory Society statement: pulmonary haemodynamics during exercise.

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term "exercise pulmonary hypertension" may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.

Recurrent Hemoptysis in Patient with Primary Pulmonary Hypertension – A Case Report and Literature Review

Pulmonary hypertension (PH) is defned as an increase in mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest as assessed by right heart catheterization (RHC). The symptoms of PH are non-specifc and mainly related to progressive right ventricular (RV) dysfunction. In some patients the clinical presentation may be related to mechanical complications of PH andthe abnormal distribution of blood flow in the pulmonary vascular bed, include hemoptysis related to rupture of hypertrophied bronchial arteries. Hemoptysis is a serious complication that is rarely reported in patients with pulmonary arterial hypertension (PAH). Hemoptysis severity ranges from mild to very severe leading tosudden death. Hemoptysis are reported to be a terminal stage ofa complication due to PAH with prevalence is variable, from 1% to 6%. Although the incidence is quite rare, the presence of recurrent hemoptysis in patients with pulmonary hypertension is a sign of poor prognosis. Bronchial artery embolization is suggested as an acute emergency procedure in the case of severe hemoptysis or as elective intervention in cases of frequent mild or moderate episodes.

Porcine model of progressive cardiac hypertrophy and fibrosis with secondary postcapillary pulmonary hypertension

BackgroundMeaningful translational large animal models for cardiac diseases are indispensable for studying disease mechanisms, development of novel therapeutic strategies, and evaluation of potential drugs.MethodsFor induction of heart failure, cardiac hypertrophy and fibrosis, a bare metal stent was implanted in the descending aorta of growing pigs (n = 7), inducing pressure stress on the left ventricle (group HYPI). The constant stent size in growing pigs resulted in antegrade partial obstruction of the aortic flow with a gradual increase in afterload. Five pigs with sham intervention served as control. Serial haemodynamic, pressure–volume loop measurements and transthoracic echocardiography (TTE) were performed to detect developing pressure overload of the LV and cardiac MRI with late enhancement for measuring LV and RV mass and ejection fraction.ResultsAt 5-month follow-up, CT and contrast aortography, and intraluminal echocardiography confirmed aortic isthmus stenosis with a mean trans-stenotic gradient of 64 ± 13.9 mmHg. Invasive haemodynamic measurements revealed a secondary increase in pulmonary artery pressure (44.6 ± 5.1 vs 25.9 ± 6.2 mmHg, HYPI vs control, p < 0.05). TTE and ex vivo analyses confirmed severe concentric LV hypertrophy (mean circumferential wall thickness, 19.4 ± 3.1, n = 7 vs 11.4 ± 1.0 mm, n = 5, HYPI vs controls, p < 0.05). The LV and RV mass increased significantly, paralleled by increased isovolumic relaxation constant (tau). Histological analyses confirmed substantial fibrosis and myocyte hypertrophy in both LV and RV. Expressions of ANP, BNP, and miRNA-29a were up-regulated, while SERCA2a and miRNA-1 were down-regulated. Plasma NGAL levels increased gradually, while the elevation of NT-proBNP was detected only at the 5-month FUP.ConclusionThese data prove that percutaneous artificial aortic stenosis in pigs is useful for inducing clinically relevant progredient heart failure based on myocardial hypertrophy and fibrosis.